Pharmacological characteristics of BDTI, a new isoquinoline-derived β2-adrenoceptor agonist, in canine trachea and rat heart

Chien-Huang Lin, Chuen Mao Yang, Chi Ming Chen, Feng Nien Ko, Che Ming Teng

研究成果: 雜誌貢獻文章

8 引文 (Scopus)

摘要

The tracheal relaxing effects and β2-selectivity of BDTI (1-benzyl-6,7-dihydroxy-1,2, 3,4-tetrahydroisoquinoline HBr) were investigated in canine trachea and rat heart by radioligand binding assay and pharmacological experiments in comparison with those of other β2-adrenoceptor agonists, salbutamol and isoprenaline. The potency of relaxing effect on carbachol-induced contraction in isolated canine trachea was in the order of isoprenaline (pD2 = 6.70 ± 0.08) > BDTI (6.11 ± 0.06) = salbutamol (6.14 ± 0.08). ICI-118,551 (a selective β2-antagonist) and atenolol (a selective β1-antagonist) inhibited the relaxant action of BDTI with pK(B) values of 8.4 and 5.3, respectively, corresponding to high affinity for ICI-118,551 and low affinity for atenolol in antagonizing this response. The K(d) values of radioligand ([3H]-CGP12177) were 453.3 ± 30.8 and 563.4 ± 96.7 pmol/l in cultured canine tracheal smooth muscle cells (TSMCs) and rat cardiomyocytes, respectively, and the B(max) values were 64.6 ± 10.7 and 245.7 ± 44.5 fmol/mg protein, respectively. BDTI, salbutamol and isoprenaline inhibited the binding of [3H]-CGP12177 in a concentration-dependent manner in cultured canine TSMCs (K(i) 0.73 ± 0.15, 0.75 ± 0.21 and 0.24 ± 0.05 μmol/l, respectively) and rat cardiomyocytes (K(i) 2.76 ± 0.36, 2.31 ± 0.26 and 0.22 ± 0.03 μmol/l, respectively). These results demonstrated that BDTI possessed moderate selectivity (3.8-fold) to β2-adrenoceptors as judged from the K(i) (heart)/K(i) (trachea) value (salbutamol 3.1-fold, isoprenaline 0.92-fold). BDTI and salbutamol also stimulated cAMP formation in a concentration-dependent manner in cultured canine TSMCs (EC50 0.5 ± 0.2 and 0.4 ± 0.1 μmol/l, respectively) and rat cardiomyocytes (EC50 6.2 ± 0.5 and 5.7 ± 0.6 μmol/l, respectively). The selectivity of BDTI and salbutamol for β2-adrenoceptors on the cAMP response were 12.4 and 14.3 times, respectively. It is concluded that BDTI is a β2-selective adrenoceptor agonist.
原文英語
頁(從 - 到)19-27
頁數9
期刊Pharmacology
53
發行號1
出版狀態已發佈 - 七月 1996
對外發佈Yes

指紋

Albuterol
Trachea
Adrenergic Receptors
Canidae
Pharmacology
Isoproterenol
Cardiac Myocytes
Smooth Muscle Myocytes
Atenolol
Radioligand Assay
Carbachol
isoquinoline
Proteins

ASJC Scopus subject areas

  • Pharmacology

引用此文

Pharmacological characteristics of BDTI, a new isoquinoline-derived β2-adrenoceptor agonist, in canine trachea and rat heart. / Lin, Chien-Huang; Yang, Chuen Mao; Chen, Chi Ming; Ko, Feng Nien; Teng, Che Ming.

於: Pharmacology, 卷 53, 編號 1, 07.1996, p. 19-27.

研究成果: 雜誌貢獻文章

Lin, Chien-Huang ; Yang, Chuen Mao ; Chen, Chi Ming ; Ko, Feng Nien ; Teng, Che Ming. / Pharmacological characteristics of BDTI, a new isoquinoline-derived β2-adrenoceptor agonist, in canine trachea and rat heart. 於: Pharmacology. 1996 ; 卷 53, 編號 1. 頁 19-27.
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title = "Pharmacological characteristics of BDTI, a new isoquinoline-derived β2-adrenoceptor agonist, in canine trachea and rat heart",
abstract = "The tracheal relaxing effects and β2-selectivity of BDTI (1-benzyl-6,7-dihydroxy-1,2, 3,4-tetrahydroisoquinoline HBr) were investigated in canine trachea and rat heart by radioligand binding assay and pharmacological experiments in comparison with those of other β2-adrenoceptor agonists, salbutamol and isoprenaline. The potency of relaxing effect on carbachol-induced contraction in isolated canine trachea was in the order of isoprenaline (pD2 = 6.70 ± 0.08) > BDTI (6.11 ± 0.06) = salbutamol (6.14 ± 0.08). ICI-118,551 (a selective β2-antagonist) and atenolol (a selective β1-antagonist) inhibited the relaxant action of BDTI with pK(B) values of 8.4 and 5.3, respectively, corresponding to high affinity for ICI-118,551 and low affinity for atenolol in antagonizing this response. The K(d) values of radioligand ([3H]-CGP12177) were 453.3 ± 30.8 and 563.4 ± 96.7 pmol/l in cultured canine tracheal smooth muscle cells (TSMCs) and rat cardiomyocytes, respectively, and the B(max) values were 64.6 ± 10.7 and 245.7 ± 44.5 fmol/mg protein, respectively. BDTI, salbutamol and isoprenaline inhibited the binding of [3H]-CGP12177 in a concentration-dependent manner in cultured canine TSMCs (K(i) 0.73 ± 0.15, 0.75 ± 0.21 and 0.24 ± 0.05 μmol/l, respectively) and rat cardiomyocytes (K(i) 2.76 ± 0.36, 2.31 ± 0.26 and 0.22 ± 0.03 μmol/l, respectively). These results demonstrated that BDTI possessed moderate selectivity (3.8-fold) to β2-adrenoceptors as judged from the K(i) (heart)/K(i) (trachea) value (salbutamol 3.1-fold, isoprenaline 0.92-fold). BDTI and salbutamol also stimulated cAMP formation in a concentration-dependent manner in cultured canine TSMCs (EC50 0.5 ± 0.2 and 0.4 ± 0.1 μmol/l, respectively) and rat cardiomyocytes (EC50 6.2 ± 0.5 and 5.7 ± 0.6 μmol/l, respectively). The selectivity of BDTI and salbutamol for β2-adrenoceptors on the cAMP response were 12.4 and 14.3 times, respectively. It is concluded that BDTI is a β2-selective adrenoceptor agonist.",
keywords = "β-adrenoceptor agonist, BDTI, Cardiomyocytes, Tracheal smooth muscle cells",
author = "Chien-Huang Lin and Yang, {Chuen Mao} and Chen, {Chi Ming} and Ko, {Feng Nien} and Teng, {Che Ming}",
year = "1996",
month = "7",
language = "English",
volume = "53",
pages = "19--27",
journal = "Pharmacology",
issn = "0031-7012",
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T1 - Pharmacological characteristics of BDTI, a new isoquinoline-derived β2-adrenoceptor agonist, in canine trachea and rat heart

AU - Lin, Chien-Huang

AU - Yang, Chuen Mao

AU - Chen, Chi Ming

AU - Ko, Feng Nien

AU - Teng, Che Ming

PY - 1996/7

Y1 - 1996/7

N2 - The tracheal relaxing effects and β2-selectivity of BDTI (1-benzyl-6,7-dihydroxy-1,2, 3,4-tetrahydroisoquinoline HBr) were investigated in canine trachea and rat heart by radioligand binding assay and pharmacological experiments in comparison with those of other β2-adrenoceptor agonists, salbutamol and isoprenaline. The potency of relaxing effect on carbachol-induced contraction in isolated canine trachea was in the order of isoprenaline (pD2 = 6.70 ± 0.08) > BDTI (6.11 ± 0.06) = salbutamol (6.14 ± 0.08). ICI-118,551 (a selective β2-antagonist) and atenolol (a selective β1-antagonist) inhibited the relaxant action of BDTI with pK(B) values of 8.4 and 5.3, respectively, corresponding to high affinity for ICI-118,551 and low affinity for atenolol in antagonizing this response. The K(d) values of radioligand ([3H]-CGP12177) were 453.3 ± 30.8 and 563.4 ± 96.7 pmol/l in cultured canine tracheal smooth muscle cells (TSMCs) and rat cardiomyocytes, respectively, and the B(max) values were 64.6 ± 10.7 and 245.7 ± 44.5 fmol/mg protein, respectively. BDTI, salbutamol and isoprenaline inhibited the binding of [3H]-CGP12177 in a concentration-dependent manner in cultured canine TSMCs (K(i) 0.73 ± 0.15, 0.75 ± 0.21 and 0.24 ± 0.05 μmol/l, respectively) and rat cardiomyocytes (K(i) 2.76 ± 0.36, 2.31 ± 0.26 and 0.22 ± 0.03 μmol/l, respectively). These results demonstrated that BDTI possessed moderate selectivity (3.8-fold) to β2-adrenoceptors as judged from the K(i) (heart)/K(i) (trachea) value (salbutamol 3.1-fold, isoprenaline 0.92-fold). BDTI and salbutamol also stimulated cAMP formation in a concentration-dependent manner in cultured canine TSMCs (EC50 0.5 ± 0.2 and 0.4 ± 0.1 μmol/l, respectively) and rat cardiomyocytes (EC50 6.2 ± 0.5 and 5.7 ± 0.6 μmol/l, respectively). The selectivity of BDTI and salbutamol for β2-adrenoceptors on the cAMP response were 12.4 and 14.3 times, respectively. It is concluded that BDTI is a β2-selective adrenoceptor agonist.

AB - The tracheal relaxing effects and β2-selectivity of BDTI (1-benzyl-6,7-dihydroxy-1,2, 3,4-tetrahydroisoquinoline HBr) were investigated in canine trachea and rat heart by radioligand binding assay and pharmacological experiments in comparison with those of other β2-adrenoceptor agonists, salbutamol and isoprenaline. The potency of relaxing effect on carbachol-induced contraction in isolated canine trachea was in the order of isoprenaline (pD2 = 6.70 ± 0.08) > BDTI (6.11 ± 0.06) = salbutamol (6.14 ± 0.08). ICI-118,551 (a selective β2-antagonist) and atenolol (a selective β1-antagonist) inhibited the relaxant action of BDTI with pK(B) values of 8.4 and 5.3, respectively, corresponding to high affinity for ICI-118,551 and low affinity for atenolol in antagonizing this response. The K(d) values of radioligand ([3H]-CGP12177) were 453.3 ± 30.8 and 563.4 ± 96.7 pmol/l in cultured canine tracheal smooth muscle cells (TSMCs) and rat cardiomyocytes, respectively, and the B(max) values were 64.6 ± 10.7 and 245.7 ± 44.5 fmol/mg protein, respectively. BDTI, salbutamol and isoprenaline inhibited the binding of [3H]-CGP12177 in a concentration-dependent manner in cultured canine TSMCs (K(i) 0.73 ± 0.15, 0.75 ± 0.21 and 0.24 ± 0.05 μmol/l, respectively) and rat cardiomyocytes (K(i) 2.76 ± 0.36, 2.31 ± 0.26 and 0.22 ± 0.03 μmol/l, respectively). These results demonstrated that BDTI possessed moderate selectivity (3.8-fold) to β2-adrenoceptors as judged from the K(i) (heart)/K(i) (trachea) value (salbutamol 3.1-fold, isoprenaline 0.92-fold). BDTI and salbutamol also stimulated cAMP formation in a concentration-dependent manner in cultured canine TSMCs (EC50 0.5 ± 0.2 and 0.4 ± 0.1 μmol/l, respectively) and rat cardiomyocytes (EC50 6.2 ± 0.5 and 5.7 ± 0.6 μmol/l, respectively). The selectivity of BDTI and salbutamol for β2-adrenoceptors on the cAMP response were 12.4 and 14.3 times, respectively. It is concluded that BDTI is a β2-selective adrenoceptor agonist.

KW - β-adrenoceptor agonist

KW - BDTI

KW - Cardiomyocytes

KW - Tracheal smooth muscle cells

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